Project 4: Brain Tumor Imaging and Therapy Using Magnetic Nanoparticles Malignant brain tumors are a particularly intractable form of cancer that has seen little survival improvement over the past few decades. The difficulty in early diagnosis of and the lack of efficient means of localizing effective therapeutic agents on the brain tumors are responsible for this clinical dilemma, which stems from the unique structure of brain vasculatures. The blood-brain barrier (BBB) in the brain vasculature consists of a continuous layer of cerebral vascular endothelial cells that are bound together with tight junctions, and prevents the access of most blood-borne agents to the brain. As a result, brain tumors are difficult to diagnose in their early stage and are among the most resistant to chemotherapy. Surgical resection or/and external radiation remains the standard treatment for brain tumors. As a part of Carolina Center of Cancer Nanotechnology Excellence (CCCNE), a team of investigators from diverse disciplines (Chemistry, Physics, Genetics, Oncology, and Radiology) at UNC-CH is assembled to apply the latest advances in nanotechnology in developing new efficient magnetic nanovectors for targeted delivery of imaging contrast agents and anticancer therapies to brain tumors. Ultrasmall superparamagnetic nanoparticles have been shown to have higher propensity of crossing the BBB owing to their unique properties. The ability to manipulate these nanoparticles with an external magnetic field offers even greater opportunities in targeted delivery to brain tumors. We will develop superparamagnetic nanoparticles with desired surface characteristics which can be directed to the brain tumors using a designer magnetic system. These nanoparticles can be further modified with a variety of cell-targeting peptides to enhance their deposition in brain tumor neovasculatures or cells. Novel brain tumor-specific multi-modality imaging contrast agents and therapeutic formulations can be readily designed based on this superparamagnetic nanoparticle platform by attaching small molecules with imaging contrast enhancement or anti-cancer properties. We will also evaluate the utility of this magnetic nanoparticle targeted delivery platform in brain tumors of a mouse model. The proposed interdisciplinary research program thus combines the latest developments in nanotechnology with new understandings of tumor biology in an effort to develop brain tumor-specific multi-modality imaging contrast agents and therapeutic formulations. The success of this project will lead to new innovative approaches to cancer research, and have significant implications in realizing early detection and developing effective therapies for brain tumors.